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Biomedical subjects

J Davidson

Publications and source records attributed to J Davidson.

At least 145 records · Page 8Linked to original sources

Alpha-melanocyte-stimulating hormone suppresses fever and increases in plasma levels of prostaglandin E2 in the rabbit.

1. The effect of alpha-melanocyte-stimulating hormone (alpha-MSH) on changes in body temperature and plasma levels of prostaglandin E2 (PGE2) were measured in the rabbit following intravenous injection of bacterial lipopolysaccharide (LPS), rabbit endogenous pyrogen (EP), human recombinant tumour necrosis factor-alpha (TNF-alpha), human recombinant interleukin-1 beta (IL-1 beta) and intracerebroventricular injection of PGE2. 2. LPS (25 ng kg-1), EP (25 microliters kg-1), TNF-alpha (11 micrograms kg-1) and IL-1 beta (5 ng kg-1) produced increases in body temperature simultaneously with increases in plasma PGE2 levels. alpha-MSH (5 or 10 micrograms kg-1) attenuated both the increase in body temperature and increases in plasma levels of PGE2. 3. Intracerebroventricular injection of PGE2 (500 ng) produced a monophasic increase in body temperature. alpha-MSH (5 micrograms kg-1) administered 20 min after PGE2 had no effect on the hyperthermic response. 4. alpha-MSH (10 micrograms kg-1) had no effect on either body temperature or plasma levels of PGE2 in response to I.V. injection of sterile saline. 5. These data demonstrate that alpha-MSH inhibits both the pyrogenic actions of LPS, EP, TNF-alpha and IL-1 beta and their ability to increase PGE2 release without affecting the direct actions of PGE2, suggesting the possibility that alpha-MSH may prevent the synthesis of PGE2 either by preventing the actions or release of mediators such as TNF-alpha and IL-1 in response to LPS.

Animals↗

Comparison of aspiration and scintigraphic techniques for the measurement of gastric emptying rates of liquids in humans.

A comparison was made of two techniques to measure the rate of gastric emptying. A noninvasive scintigraphic technique using a gammacamera and an invasive aspiration technique based on dye dilution were performed simultaneously. Seven healthy male volunteers each consumed two different liquid meals on two separate occasions. Scintigraphic measurements were performed continuously with aspiration every 10 minutes for a total of one hour. Gastric emptying rates were expressed as slope values after semilog linearisation of the emptying curves. Agreement between the two methods was assessed from the individual differences and mean of the two techniques, as well as from the geometric mean, including 95% limits of agreement. The scintigraphic technique gave a 70% slower emptying rate than the dye dilution technique. However, the 95% limits of agreement are large (1.56 to 0.30), reflecting the small sample size and the large coefficient of variation in the techniques used.

Adult↗

Regional mapping of a liver alpha-subunit gene of phosphorylase kinase (PHKA) to the distal region of human chromosome Xp.

X-linked liver glycogenosis (XLG) is a glycogen storage disorder resulting from deficient activity of phosphorylase kinase (PHK). PHK consists of four different subunits: alpha, beta, gamma, and delta. Several genes encoding PHK subunits have been cloned and localized, but only the muscle alpha-subunit (PHKA) gene has been assigned to the X chromosome, in the region Xq12----q13. However, we have previously excluded the muscle PHKA gene as a candidate gene for the XLG mutation, as linkage analysis indicated that the mutation responsible for XLG is located in Xp22 and not in Xq12----q13. We report here the chromosomal localization by in situ hybridization of a liver PHKA gene to the distal region of chromosome Xp. Strong hybridization signals were observed on the distal part of the short arm of a chromosome identified as the X chromosome by cohybridization with an X chromosome-specific centromeric probe. The localization of this gene in the same chromosomal region as the disease gene responsible for XLG suggests that the liver PHKA gene is a highly likely candidate gene for the XLG mutation.

Chromosome Mapping↗

Drug therapy of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a recently introduced diagnosis. The disorder is quite common, yet often unrecognised, and leads to significant morbidity or mortality. Effective treatment often entails use of psychotropic medication. Only recently has this become apparent, and awareness of the role of drug therapy in PTSD remains limited. A number of studies have indicated efficacy for antidepressant, mood-stabilising, anticonvulsant and antianxiety medications. This review describes the role of pharmacotherapy, by examining issues of diagnosis and recognition of PTSD, the theoretical basis for drug use, goals of drug treatment, dose ranges, and clinical application of psychotropic drugs.

Animals↗

Juvenile angiofibroma: a review of the literature and a case series report.

Juvenile angiofibroma is a rare, histologically benign tumor which occurs almost exclusively in adolescent boys. The morbidity and mortality associated with this tumor are related to its prominent vascularity and its propensity for aggressive local growth. From 1974 through 1988, 21 male patients with a diagnosis of juvenile angiofibroma were managed at the Toronto General Hospital or the Hospital for Sick Children, Toronto. Preoperative computed tomography was performed on 20 patients, selective angiography on 21 patients, and preoperative embolization on 15 patients. Primary surgery was performed on 67% of these patients, with radiation therapy used for advanced stage II and stage III disease or in response to patient preference. Pterygopalatine fossa involvement was demonstrated in 90% of the patients; as a result, the lateral rhinotomy approach was most commonly used in the surgical cases. A successful outcome was achieved in 86% of patients treated with surgery alone. Two patients underwent radiotherapy for salvage following postoperative recurrence. There were no treatment-related deaths and no major surgical complications. The value of computed tomography is discussed, the authors' treatment protocol is outlined, and the case series results are presented.

Adolescent↗

Differential sensitivity of CD34 epitopes to cleavage by Pasteurella haemolytica glycoprotease: implications for purification of CD34-positive progenitor cells.

Our previous studies have shown that a unique glycoprotease from Pasteurella haemolytica specifically cleaves only proteins containing sialylated O-linked glycans. The hematopoietic progenitor cell antigen, CD34, which is heavily glycosylated with both N- and O-linked glycans, is readily cleaved by this protease. In this study, we demonstrate that the epitopes detected by five of the seven CD34 monoclonal antibodies are removed by the glycoprotease. The differential sensitivity of the CD34 epitopes to cleavage with either neuraminidase and/or glycoprotease establishes three classes of epitopes: 1) (class I) those identified by MY10, B1.3C5, 12.8, and ICH3 that are differentially affected by neuraminidase and removed by the glycoprotease; 2) (class II) the epitope detected by QBEND 10 that is removed only by the glycoprotease; and 3) (class III) those identified by TUK3 and 115.2 that are not removed by either enzyme. Cleavage of the 110-kd CD34 structure by the glycoprotease generates a major cell-bound fragment of about 75 kd, identified by the class III antibodies. We have also used the enzyme to improve the rapid recovery of CD34+ cells selected by immunomagnetic affinity techniques. In a preclinical model, we separated CD34+ KG1 cells with high yield (90%-95%) and high purity (94%-98%) from sham mixtures containing 50% CD34- cells. We also separated CD34+ blast cells from a patient in megakaryoblastic crisis of chronic myelogenous leukemia. In this case, the purity and yield were 93% and 94%, respectively. Enzyme treatment had no detrimental effect on cell viability, and the treated cells showed a normal quantitative expression and distribution of CD34 antigen as assessed with class III antibodies. We conclude that the P. haemolytica glycoprotease has potential to improve the isolation, from human bone marrow, of primitive hematopoietic cells that carry the CD34 antigen.

Antigens, CD↗

Retention of progenitor cell function in CD34+ cells purified using a novel O-sialoglycoprotease.

We previously showed that the sialoglycoprotein, CD34, which is expressed on primitive human hematopoietic progenitor cells, is cleaved by a unique glycoprotease from Pasteurella haemolytica (P.h. glycoprotease). This proteolytic enzyme specifically cleaves glycoproteins rich in O-sialoglycans. Glycoproteins containing only N-linked glycans are not cleaved. Cleavage of the CD34 antigen results in the loss of epitopes detected by five of seven CD34-designated antibodies. In this study, we investigated the role of the P.h. glycoprotease in isolating CD34+ cells from unfractionated normal human bone marrow mononuclear cells (MNCs), and determined the effect of the glycoprotease on the proliferative capacity of the progenitor-enriched fraction. CD34+ cells were isolated from MNCs using immunomagnetic beads attached via a CD34 antibody whose epitope is susceptible to removal by the cleavage with the glycoprotease. Subsequent cleavage with P.h. glycoprotease for 30 min at 37 degrees C released the CD34+ cells from the beads with a recovery of up to 78%. Using a CD34 antibody whose epitope was not removed by the glycoprotease, up to 95% of the recovered cells expressed CD34. Compared to unseparated MNCs, the CD34+ cells showed the following enrichment of committed hematopoietic progenitors, as assayed in semi-solid media: CFU-GM, 45-fold; CFU-M, 13-fold; BFU-E, 26-fold and CFU-GEMM, 81-fold. Hematopoiesis was also studied in two-stage long-term bone marrow cultures in which the CD34+ cells were co-cultured over irradiated, allogeneic adherent layers. Output of CFU-GM over a seven week period from these cultures was similar to that from control cultures with autologous adherent-cell-depleted marrow MNCs. These data suggest that the loss of O-sialo-glycosylated peptide moieties from P.h. glycoprotease-released CD34+ cells neither affects the functional capacity of committed progenitors, nor impairs the proliferation of long-term culture-generating cells. The P.h. glycoprotease can be used to facilitate the isolation and recovery of functionally competent CD34+ cells at high yield and purity, without prior removal of other adherent cells. The ability to rapidly purify CD34+ cells using this non-cytotoxic enzyme has important implications for bone marrow transplantation as well as for gene transfer studies in vitro.

Antigens, CD↗

A comparison of the results following oromandibular reconstruction using a radial forearm flap with either radial bone or a reconstruction plate.

Fifteen cases of oromandibular reconstruction using a radial osteocutaneous flap were compared with 16 in which the mandible was replaced with a reconstruction plate and a forearm flap was used for intraoral lining. All cases involved oral cancer; most had been irradiated. Nine survived in each group. Complications included one infected nonunion in addition to two bone exposures in the bone group, compared with three cases of plate exposure and two bone exposures in the plate group. Functional results were similar in both, but osteointegrated implants were possible only in the patients receiving bone. Cosmesis seemed somewhat better in the plate group. Donor-site problems were common but minor, and long-term forearm function was slightly reduced in both groups. Although the sample sizes were small, the reconstruction plate together with a radial forearm flap appeared to provide effective reconstruction following composite resection. However, we would not recommend this for the younger patient or in benign disease.

Adult↗

Antipyretic actions of human recombinant lipocortin-1.

The effect of human recombinant lipocortin-1 (hrLC-1) on the pyrogenic actions of the synthetic polyribonucleotide polyinosinic:polycytidylic acid (poly I:C) has been studied in conscious rabbits. Poly I:C (2.5 micrograms kg-1) given i.v. produced a biphasic fever with a first peak after 90-105 min and a second peak between 225-240 min. hrLC-1 (50 micrograms kg-1) given i.v. simultaneously with the poly I:C produced a significant reduction in the febrile response but without complete suppression. The thermal response index over 5 h (TRI5) was 4.69 +/- 0.51 for poly I:C given with saline and the TRI5 for poly I:C given with hrLC-1 was 2.66 +/- 0.45 (values are for n = 5 +/- s.e. mean, P less than 0.05). hrLC-1 administered alone had no effect on body temperature and its antipyretic activity was lost on heating. In a separate series of experiments 1 h pretreatment with dexamethasone (1 mg kg-1) given i.v. reduced the pyrogenic response (TRI5) to poly I:C (2.5 micrograms kg-1) from 4.87 +/- 0.54 without dexamethasone to 2.00 +/- 0.25 (n = 5, P less than 0.05) and dexamethasone given alone had no effect on body temperature. These data demonstrate that LC-1 possesses antipyretic actions and raises the possibility that the antipyretic actions of dexamethasone are mediated through the induction of LC-1.

Animals↗

A psychodynamic perspective on the clinical impact of insurance review.

The rise of managed care and concurrent utilization review has had a profound impact on the practice of inpatient psychiatry. Little has been written, however, on the clinical impact of the review process itself. The actions of insurance reviewers often result in their being incorporated into the psychopathology of individual patients and into the dynamics of families and institutional settings. The authors apply psychodynamic understanding to a series of case examples to illustrate how concurrent review may promote splitting, impede the patient's ability to separate from the hospital, and paradoxically reinforce the patient's illness. They also explore a number of typical responses of treatment staff and families to the review process. A case vignette demonstrating a sincere effort at mutual collaboration between payers and providers is also presented. This spirit of compromise is proposed as the solution that best serves patient care.

Adolescent↗

A 102-center prospective study of seizure in association with bupropion.

BACKGROUND: This trial was conducted to determine the incidence of seizures associated with the use of bupropion. METHOD: A total of 3341 depressed patients from 102 sites were enrolled in this 8-week, prospective, open trial. Following the 8-week treatment phase, patients could elect to enroll in a humanitarian continuation phase of unlimited duration. Dosing was initiated at 225 mg/day and increased to 450 mg/day as tolerated. Investigators carefully monitored seizure occurrences and rated their patients' response to and tolerance of bupropion. RESULTS: A total of 1986 patients (61%) completed the 8-week treatment phase, and 1616 (81%) of these elected to be maintained on bupropion treatment in the humanitarian continuation phase. The observed seizure rate was 0.24% for the treatment phase and 0.40% for the entire study. An 8-week survival analysis performed on patients with a dosing regimen of 300 to 450 mg/day yielded a cumulative rate of 0.36%. Patients, including those previously resistant to antidepressant treatment, responded to and tolerated bupropion well. CONCLUSION: These rates confirm earlier seizure estimates and fall within accepted parameters for antidepressant drugs. This trial enhances bupropion's position as a valuable alternative for the management of depression.

Adolescent↗

A-O plate mandibular reconstruction: a complication critique.

Immediate A-O plate mandibular reconstruction was used in 31 patients, following the excision of malignant disease. This five-year retrospective study shows that 48% (15/31) of the patients are living (one with recurrence), with a mean follow-up of 30 months (range nine to 60 months). The mean survival of the deceased patients was 11 months (range two weeks to 46 months). Postoperative complications are evaluated with respect to the mandibular defect, radiation status, dentition, adjuvant onlay bone grafting and T stage. Briefly, 11/31 patients (36%) enjoyed an uneventful recovery, 9/31 (29%) developed a minor wound complication, 6/31 (19%) developed a major wound complication and 5/31 (16%) had significant aspiration. Four plates were removed and an additional three plates were exposed. In general, those patients in whom the condylar head was removed, or in whom the mandibular resection crossed the midline, experienced more wound complications (67% vs. 37%). Simultaneous onlay bone grafting almost doubled the complication rate and this reconstructive technique has been abandoned. No significant contribution to complication rate was made by radiation status, T stage or dentition in our patient population. In addition, four plates have been uneventfully irradiated postoperatively, and five patients have been successfully fit with dentures over their reconstruction plates.

Adult↗

Treatment of posttraumatic stress disorder with amitriptyline and placebo.

Amitriptyline hydrochloride was compared with placebo in 46 veterans with chronic posttraumatic stress disorder. Treatment continued up to 8 weeks, and efficacy was measured by five observer and two self-rated scales. Percent recovery rates were higher for amitriptyline than placebo on two measures. In patients who completed 4 weeks (n = 40), better outcome with amitriptyline was noted on the Hamilton depression scale only. In the group completing 8 weeks of treatment (n = 33), the drug was superior to placebo on Hamilton depression, Hamilton anxiety, Clinical Global Impression severity, and Impact of Event scales. There was no evidence for drug effects on the structured interview for posttraumatic stress disorder. Drug-placebo differences were greater in the presence of comorbidity in general, although recovery rates were uniformly low in the presence of major depression, panic disorder, and alcoholism. At the end of treatment, 64% of the amitriptyline and 72% of the placebo samples still met diagnostic criteria for posttraumatic stress disorder.

Ambulatory Care↗

The risk of developing subsequent nonmelanoma skin cancers.

Data from the Southeast Arizona Skin Cancer Registry collected during 1985 through June 1988 were used in this study. Patients who had a nonmelanoma skin cancer (basal cell or squamous cell carcinoma) removed in 1985 were observed until subsequent nonmelanoma skin cancers developed or until June 30, 1988. Twelve categories of nonmelanoma skin cancers were developed on the basis of the type of first nonmelanoma skin cancer and type of second, third, and fourth nonmelanoma skin cancers. Analyses showed the highest risk of a subsequent nonmelanoma skin cancer developing was within 1 year (36.39%), the rate of developing another nonmelanoma skin cancer depended on type (squamous cell carcinoma, 100%; basal cell carcinoma, 44.23% to 83.65%), and total risk decreased during the 1277 days of the study.

Aged↗